CURRENT SCIENCE REVIEWS By Joe Bruman November 1997 p. 1 of 4 Tedeschi G et al; Brain 1997;120:1541-1552: They scanned 12 patients with progressive supranuclear palsy, 10 with Parkinson's disease, 9 with corticobasal degeneration, and 11 healthy controls, by proton magnetic resonance imaging. Mapping the distribution of certain compounds by that technique can distinguish PD from PSP or CBGD. Gerloff C et al; Brain 1997;120:1587-1602: Transcranial magnetic stimulation of the supplementary motor area of the frontomesial cortex interferes with preparation for planned complex movement sequence. Lancet, 20 Sep 1997;868 (news item): Debate continues over grafting animal tissue or organs into humans. Breeding of genetically altered pigs has resolved the hyperacute rejection problem, but the porcine endogenous retrovirus still might produce new pathogens transmissible by humans. Gross C et al; J Neurosurg 1997;87:491-498: Chronic implanted stimulation of the globus pallidus internus in 7 late-stage PD patients alleviated akinesia, rigidity, and levodopa- induced dyskinesia, improved gait and speech impairment, and in some subjects reduced tremor, for follow-up periods up to 3 years. The "high frequency" was 135 to 185 Hz. Albanese A et al; Mov Disord 1997;12:764-766: Local injection of botulinum toxin relieved severe constipation in a PD patient. Le Couteur D et al; Mov Disord 1997;12:760-763: A certain anomaly in the dopamine transporter gene was 10 times more common among 100 PD patients than in 200 controls. Since the dopamine transporter mediates susceptibility to MPTP, they suspect that the genetic anomaly might also cause susceptibility to PD. Hauser R, Zesiewicz T; Mov Disord 1997;12:756-759: They tried the serotonin reuptake inhibitor Sertraline in 15 PD patients with depression. It helped but had adverse effects, worse for those on selegiline, on 5 of the subjects, 2 of whom quit. Schuurman P et al; Mov Disord 1997;12:752-755: Staged bilateral posteroventral pallidotomy in 3 young-onset patients with advanced (H-Y stage 5) PD. One had visual field deficit and transient facial paresis, but overall improvement of response fluctuations, hypokinesia, rigidity, and dystonia was marked and lasting, up to the longest follow-up of 13 months. Strafella A et al; Mov Disord 1997;12:727-737: A single stimulus through an implanted electrode inhibited specific voluntary movement if the site was the ventrolateral thalamus, but not the periventricular grey matter, globus pallidus internus, or subthalamic nucleus, leading to a hypothesis about the pathway involved in the parkinsonian rest tremor. Rosin R et al; Mov Disord 1997;12:682-690: They used an optoelectronic tracking system to study gait kinematics in 31 PD patients and 20 healthy controls, finding the overall pattern similar, but preparation phase longer, in the PD group. CURRENT SCIENCE REVIEWS By Joe Bruman November 1997 p. 2 of 4 Pahwa R et al; Mov Disord 1997;12:677-681: In a short study to compare effects of Sinemet CR against those of regular Sinemet in 18 PD patients at the fluctuation stage, they needed more CR to compensate its reduced absorption, but enjoyed better home management and mobility. Konczak J et al; Mov Disord 1997;12;665-676: They studied the effect of external timing signals on repetitive voluntary movement in 12 PD patients, finding that it might help initiation, but not temporal or spatial coordination. Teo C et al; Mov Disord 1997;12:655-664: They found decreased habituation of auditory evoked responses in advanced-PD patients, and conclude that PD may cause disregulation of sensory processing. Curra A et al; Mov Disord 1997;12:646-654: In a test having subjects point to sequential targets on a screen, PD patients were slower, more so in internally determined than in externally cued movements. Kosel S et al; Mov Disord 1997;12:639-645: PD is characterized by defect in the respiratory chain of neural mitochondria. However, in postmortem analysis they found no corresponding defect in mitochondrial DNA. Rajput A et al; Mov Disord 1997;12:634-638: They report 5 patients who had large cumulative dosage of levodopa (up to 24 kg in 26 yr). Three had essential tremor, one had dopa- responsive dystonia, and one had non-progressive parkinsonism. None, including 2 autopsied, showed evidence of levodopa neurotoxicity. Jaber M et al; Mov Disord 1997;12:629-633: They used a strain of genetically altered mice to demonstrate the central importance of the plasma membrane dopamine transporter in regulating dopamine level in the brain and as an obligatory target for the action of amphetamine and cocaine. They suggest further study of transporter-affecting drugs. Durr A et al; J Neur N'surg Psych 1997;63:394-395: They studied DNA of 57 with familial PD, 46 with idiopathic PD, and 387 healthy controls, for genes of variants of apolipoprotein E, one of which is a feature of Alzheimer's. That one is not significant in PD, but they found another which distinguishes familial from sporadic PD. Komaroff A: JAMA, 8 Oct 97:1179-1185: Complete detailed case history of a 56-yr woman with severe disabling chronic fatigue for 11 yr. She reported at times feeling unable to get out of bed in the morning; profound fatigue, pain, and weakness after minor exertion. Various soporific and antidepressant drugs were ineffectual, and at time of review, neither attending physician nor commentator knew what to do next. At one point, he mentions "she walked slowly", and "family history remarkable for Parkinson disease" but, incredibly, fails to mention PD anywhere else in the 7-page article. CURRENT SCIENCE REVIEWS By Joe Bruman November 1997 p. 3 of 4 Bain P; The Neurologist 1997;3:305-321: In this rather new journal aimed at neuros in clinical practice, the most thorough (217 refs) summary and tutorial yet seen on essential tremor. All the known treatments, with histories and actual trial results. Sanberg P et al; Nat Med 1997;3:1129-1132: Ethical and logistic problems of fetal tissue inspire a search for other sources of dopaminergic cells. A promising candidate is the Sertoli cells of the testis, readily obtainable from adult cadavers or pigs rather than aborted human fetuses, and which have improved parkinson symptoms in rat experiments. Eliasson M et al; Nat Med 1997;3:1089-1095*: The unhappy feature of ischemic stroke is the death of involved neurons, blamed in part on excess nitric oxide (NO) and glutamate, which happen also to be suspected villains in PD. Working with mice, researchers found that inhibiting the mediator poly(ADP-ribose) polymerase (PARP), or deleting the gene for it, is neuroprotective. * comment, 1073-1074 Science News; 18 Oct 1997:255 (news item): Lewy bodies, a hallmark of PD, are found to be clumps of the protein alpha-synuclein. Although it isn't certain that Lewy bodies cause the death of brain cells, scientists are looking for ways to prevent alpha-synuclein from clumping. Haas H et al; J Neur N'surg Psych 1997;63:421-428: In formal trial of tolcapone and tolcapone plus levodopa in late-stage PD patients having "wearing-off" motor fluctuations, tolcapone prolonged "on" time, shortened "off" time, and reduced the levodopa dosage requirement. Oliveira R et al; J Neur N'surg Psych 1997;63:429-433: Small handwriting common in PD was improved by external cues, either auditory reminders or guiding marks on the paper. Movements became generally longer rather than faster. Graham J et al; J Neur N'surg Psych 1997;63:434-440: Hallucinations in PD are associated with direct-acting dopamine agonists, but not with age at onset or levodopa dosage amount. However the 129-patient survey showed two distinct modes: in early stages, association with rapid progression and lack of cognitive impairment; and in late (>5 yr) stages, with cognitive impairment. Jansek R, Morris M; J Neur N'surg Psych 1997;63:556: Improvement of gait in PD is better done by attention to stride length than to faster cadence. Guttman M et al; Neur 1997;49:1060-1065: Comparison of pramipexole vs. bromocriptine vs. placebo in 247 late-stage (fluctuating) PD patients showed pramipexole somewhat better than bromocriptine, and much better than placebo. Rajput A et al; Neur 1997;49:1066-1071: Formal trial on 247 fluctuating PD patients showed that tolcapone improves motor function and reduces levodopa requirement. CURRENT SCIENCE REVIEWS By Joe Bruman November 1997 p.4 of 4 Uitti R et al; Neur 1997;49:1072-1077: In 20 consecutive pallidotomy recipients about equally divided between under 65 and over 65, the elderly benefited as well as the younger group. Troster A et al; Neur 1997;49:1078-1083: Although some pallidotomy recipients have had decline in memory and language, 9 recipients of pallidal stimulation implants had no such problems. Kazumata K et al; Neur 1997;49:1083-1090: Careful clinical, PET, and MRI study of 22 pallidotomy recipients showed that glucose metabolism in the lentiform nucleus, and clinical responsiveness to levodopa, may be useful predictors of subsequent pallidotomy benefits. Richard I et al; Neur 1997;49:1168-1170: In a survey, 71 investigators reported that 26% of 23,410 PD patients were on antidepressants. Although selective serotonin reuptake inhibitors {e.g., Paxil, Prozac, Zoloft) are popular, there is some fear that they may aggravate motor impairment, and authors suggest a controlled trial. Denson M et al; Ann Neur 1997;42:638-643: They studied a newly found PD cluster in a family of Mennonites who migrated together from Germany to Poland to the Crimea, and late in the 19th century to America. Their PD is distinct, both clinically and pathologically, from that of previously reported PD kindreds. Zareparsi S et al; Ann Neur 1997;42:655-658: Features of PD and AD sometimes overlap. A mutation of the gene for apolipoprotein E is associated with Alzheimer's, and now in 137 PD patients, the same mutation is associated with early onset of PD. Le Tissier P et al; Nature, 16 Oct 97:681-682 and: Lancet, 18 Oct 97:1148 (news item): A retrovirus survives by invading and corrupting its host DNA, thus ensuring its transmission from one generation to the next. Some RVs cause illness in the host; others are harmless to the host but may cause illness in humans or other species. Two such dangerous RVs were found in pigs, and it looks unlikely that they can be bred out; so the future of pig cell transplants in PD for now seems bleak. Bandmann O et al; Lancet, 18 Oct 97:1136-1139: Pursuing the notion of inherited susceptibility to environmental PD hazards, they looked at 6 genes for enzymes that reduce environ- mental toxins, in 100 patients with sporadic PD, 100 with familial PD, and brain tissue of 100 PD-free controls. Of the 6 they found one having much more frequent mutations in, and therefore associated with, the familial PD group. Le Bars P et al; JAMA, 22 Oct 97:1327-1332: A 52-week double-blind trial of Ginkgo Biloba extract in 202 patients with dementia from either Alzheimer's or multiple infarcts (applicable to PD) showed a modest but distinct improvement in cognition. J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013